The Vanderbilt Alliance for Nanomedicine is a multi-institutional, multi-disciplinary alliance established in early 2004 between Vanderbilt University Medical Center, Vanderbilt University, and the Oak Ridge National Laboratory. The Alliance is focused on the use of emerging nanotechnologies for discoveries about the molecular and cellular basis for immunity and immunomodulation. The mammalian strategy for defense against foreign invaders is a highly integrated system in which every cell type of the body exhibits the capacity to relay danger signals to the immune surveillance system, raising the alarm through the production of chemotactic cytokines and other messengers that recruit specific inflammatory cells to target tissues. This warning system is highly regulated at many levels so that the kinetics and type of local tissue response is appropriate for the particular invading microorganism. The three major scientific programs in the proposed nanomedicine center focuses on detailing the signaling networks in three phases of the immune response to viruses: epithelial cell interactions, dendritic cell activation and antigen presentation, and B and T cell adaptive immune responses. Unique tools such as functionalized nanoparticles, nanowires, and nanofluidic devices such as nanphysiometers are now available in our Alliance to study these three phases of immune response in comprehensive detail with a systems biology approach at the single cell level. Our cell biologists and immunologists will using emerging nanotechnologies developed by nanotechnology scientists to study immune responses on the nanoscale in single cells. The results of experiments will be analyzed using unique computational resources and biomathematical modeling capabilities. We will apply these new technologies to immune cells, first in order to discover in detail how particular immune receptor systems function, and ultimately to manipulate immune responses in cells or in vivo at the single cell level. The Vanderbilt Alliance for Nanomedicine also will serve four unique roles as a node in the Nanomedicine network, interacting with other centers: 1. Immunology and infectious diseases. 2. Materials science, especially nanoparticles, nanowires, and nanofluidics. 3. Instrumented platforms for cellular imaging and control. 4. Biocomputing.